title: Distribution of lethal giant larvae (Lgl) protein in the tegument and negative impact of siRNA-based gene silencing on worm surface structure and egg hatching in Schistosoma japonicum.
abstract: Lethal giant larvae (Lgl) are an evolutionarily conserved tumor suppressor present in fungi and animals. It plays an essential role in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. Here, we report the presence of Lgl gene in the blood fluke Schistosoma japonicum (SjLgl) (GenBank: KF246684). SjLgl protein was mainly distributed in the unique surface tegument structure by immunofluorescence microscopic staining. Using a simple soaking method, a short interfering RNA (siRNA)-based RNA interference approach knocked down the expression of SjLgl in schistosomula in vitro by up to 89.0%. Moreover, tail vein injection of SjLgl-siRNA into the infected mice reduced SjLgl mRNA levels in vivo by 48.6-85.3%, depending on the duration of treatments. SjLgl-specific siRNA treatment during the infection in mice significantly altered the surface structure of adult worm, featured by the disappearance or significant reduction of sharp spines on the inner all of oral and ventral suckers. The siRNA also reduced the hatching rates in eggs produced by treated mice by up to 85.3%. These observations implied that Lgl plays an important role in the development of tegument in schistosomes, and may be explored as a novel target for developing immuno- and/or small molecule-based therapeutics to control and treat the infections caused by schistosome and other flatworms.
authors.affiliation: Key Laboratory of Animal Parasitology, Ministry of Agriculture of China, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 518, Ziyue Road, Shanghai, 200241, China.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Cao
authors.forename: Yanli
authors.initials: Y
authors.lastname: Shi
authors.forename: Hongbin
authors.initials: H
authors.lastname: Qiao
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Yang
authors.forename: Jinming
authors.initials: J
authors.lastname: Liu
authors.forename: Yaojun
authors.initials: Y
authors.lastname: Shi
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Lin
authors.forename: Guan
authors.initials: G
authors.lastname: Zhu
authors.forename: Yamei
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010063:Ovum / Q000502:physiology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D017208:Rats, Wistar; D012549:Schistosoma japonicum / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015801:Helminth Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins